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Alkene/Alkane-Bridged Mimics of the Lantibiotic Nisin: Toward Novel Peptide-Based Antibiotics

  • Rianne A. G. Harmsen
  • Nourdin Ghalit
  • Johan Kemmink
  • Hans W. Hilbers
  • Eefjan Breukink
  • Dirk T. S. Rijkers
  • Rob M. J. Liskamp
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

Nisin belongs to a class of natural antimicrobial peptides, the lantibiotics, which is produced by a broad range of bacteria e.g. Bacillus, Lactococcus, Streptomyces and Staphylococcus species [1]. A general feature of these peptides is the presence of a lanthionine moiety (thioether- or sulfide bridge) which gives these peptides their specific bioactive conformation.

Nisin binds with its N-terminus to lipid II thereby enabling the C-terminus to form pores in the phospholipid membrane which ultimately leads to cell leakage and causes a collapse of the vital ion gradients across the cell membrane. Lipid II is an important target for many antimicrobial peptides such as vancomycin, ramoplanin and nisin and serves as a general target for the development of new antibiotics [2].

Recently, the molecular mechanism of the nisin — lipid II interaction has been unraveled by NMR studies [ 3]. It has been found that nisin binds the pyrophosphate moiety in the pyrophosphate cage which...

Keywords

Antimicrobial Peptide Large Unilamellar Vesicle Bioactive Conformation Covalent Constraint Terminal Alkene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Rianne A. G. Harmsen
    • 1
  • Nourdin Ghalit
    • 1
  • Johan Kemmink
    • 1
  • Hans W. Hilbers
    • 1
  • Eefjan Breukink
    • 2
  • Dirk T. S. Rijkers
    • 1
  • Rob M. J. Liskamp
    • 1
  1. 1.Medicinal Chemistry & Chemical Biology, Utrecht Institute for Pharmaceutical Sciences Department of Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands
  2. 2.Chemical Biology & Organic Chemistry, Department of Chemistry, Faculty of SciencesUtrecht UniversityUtrechtThe Netherlands

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